OBJECTIVE To determine the role of endogenous carbon monoxide(CO) in oxidant-mediated organ injury following limb ischemia-reperfusion (I/R) in rats. METHODS: Sixty-four SD rats were divided into 4 groups: Sham group, Sham + zinc protoporphyrin (ZnPP, an inhibitor of heme oxygenase activity), 2-hour ischemia followed by 4-hour reperfusion (I/R) group and I/R + ZnPP group. Carboxyhemoglobin (COHb) level in the artery blood, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the lung, heart, liver and kidney were detected. The 24-hour survival rate of rats was studied. RESULTS: Compared with the sham group, the COHb level and MDA content significantly increased, while the SOD activity and the survival rate significantly decreased in I/R group (P lt; 0.05). Compared with the I/R group, MDA content significantly increased, while the SOD activity, the 24-hour survival rate and COHb level significantly decreased in I/R + ZnPP group (P lt; 0.05, respectively). CONCLUSION: Limb I/R could lead to the oxidant-mediated multiple organ injury accompanied by the increase of CO level which play an important role in the defense against I/R-induced remote multiple organ injury in rats.
【 Abstract 】 Objective To investigate the effects of 250 ml/m3 carbon monoxide (CO) inhalation or intraperitoneal infusion on lipopolysaccharide (LPS) induced rat intestinal tract injury, and to detect the roles of p38 mitogen-activated protein kinase (MAPK) pathway during CO administration. Methods After received 5 mg/kg LPS or an equal volume of normal saline by intravenous injection, 108 male SD rats were randomly divided into 6 groups: control group, CO inhalation (250 ml/m3) group, CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group, LPS (5 mg/kg) group, LPS (5 mg/kg)+CO inhalation (250 ml/m3) group and LPS (5 mg/kg)+CO intraperitoneal infusion (250 ml/m3 at a rate of 2 L/min) group. The animals were differently sacrificed at 1, 3 and 6 h for the observation, and the ileum tissues were homogenized for determination the levels of platelet activator factor (PAF), intercellular adhesion molecule-1 (ICAM-1) and interlukin-10 (IL-10) with enzyme-lined immunosorbent assay, the content of maleic dialdehyde (MDA) with thiobarbitric acid, the activity of myeloperoxidase (MPO) with chemical method, the activity of superoxide dismutase (SOD) with hydroxylamine, the activity of phosphorylated p38 MAPK with Western blot, the pathology with light microscope, and the extents of cell apoptosis were showed by the ratio of the apoptotic cells which had less DNA to the total cells of a cell-suspension sample by using the flow cytometry after being stained with propidium iodide. Results Compared with both control, CO inhalation and intraperitoneal infusion group at the same time point, the levels of PAF, ICAM-1, MDA, MPO, cell apoptosis rate and the phosphorylated p38 MAPK protein in LPS group were increased, while IL-10 and SOD were decreased (P ＜ 0.05 or 0.01), and accompanied by severe intestinal tract injury. There were no statistics differences at the different time point in the same group. PAF, ICAM-1, MDA, MPO and cell apoptosis rate in both LPS+CO inhalation group and LPS+CO intraperitoneal infusion group were lower, while IL-10 and SOD were higher than the corresponding value in LPS group at the same time point (all P ＜ 0.05), with ameliorate injury too, but the expression of phosphorylated p38 MAPK was further up-regulated than that of LPS group (all P ＜ 0.05). However, there were no significant differences in these parameters between LPS+CO inhalation group and LPS+CO intraperitoneal infusion group. Conclusion 250 ml/m3 CO inhalation and intraperitoneal infusion exerts the similar protection against LPS induced rat intestinal tract injury via anti-oxidant, anti-inflammation, and anti-apoptosis. This may involve the p38 MAPK pathway.
Objective To construct a nomogram model for predicting delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) in emergency departments. Methods All patients with acute carbon monoxide poisoning who visited the Department of Emergency of Zigong Fourth People’s Hospital between June 1st, 2011 and May 31st, 2023 were retrospectively enrolled and randomly divided into a training set and a testing set in a 6∶4 ratio. LASSO regression was used to screen variables in the training set to establish a nomogram model for predicting DEACMP. The discrimination, calibration, and clinical practicality were compared between the nomogram and Glasgow Coma Scale (GCS) in the training and testing sets. Results A total of 475 patients with acute carbon monoxide poisoning were included, of whom 41 patients had DEACMP. Age, GCS and aspartate aminotransferase were selected as risk factors through LASSO regression, and a nomogram model was constructed based on these factors. The areas under the receiver operating characteristic curves for nomogram and GCS to predict DEACMP in the training set were 0.897 [95% confidence interval (CI) (0.829, 0.966)] and 0.877 [95%CI (0.797, 0.957)], respectively; and those for nomogram and GCS to predict DEACMP in the testing set were 0.925 [95%CI (0.865, 0.985)] and 0.858 [95%CI (0.752, 0.965)], respectively. Compared with GCS, the performance of nomogram in the training set (net reclassification index=0.495, P=0.014; integrated discrimination improvement=0.070, P=0.011) and testing set (net reclassification index=0.721, P=0.004; integrated discrimination improvement=0.138, P=0.009) were both positively improved. The calibration of nomogram in the training set and testing set was higher than that of GCS. The decision curves in the training set and testing set showed that the nomogram had better clinical net benefits than GCS. Conclusion The age, GCS and aspartate aminotransferase are risk factors for DEACMP, and the nomogram model established based on these factors has better discrimination, calibration, and clinical practicality compared to GCS.